Recombinant Human Tumor Necrosis Factor-$\alpha $: Effects on Proliferation of Normal and Transformed Cells in vitro

Modulation of the growth of human and murine cell lines in vitro by recombinant human tumor necrosis factor-$\alpha $ (rTNF-$\alpha $) and recombinant human interferon-$\gamma $ (rIFN-$\gamma $) was investigated. rTNF-$\alpha $ had cytostatic or cytolytic effects on only some tumor cell lines. When administered together with rIFN-$\gamma $, rTNF-$\alpha $ showed enhanced antiproliferative effects on a subset of the cell lines tested. In contrast to its effects on sensitive tumor cells, rTNF-$\alpha $ augmented the growth of normal diploid fibroblasts. Variations in the proliferative response induced by rTNF-$\alpha $ were apparently not due to differences in either the number of binding sites per cell or their affinity for rTNF-$\alpha $. These observations indicate that the effects of rTNF-$\alpha $ on cell growth are not limited to tumor cells, but rather that this protein may have a broad spectrum of activities in vivo.